The 2009 H1N1 influenza pandemic response was the fastest global vaccine development effort in history. Within six months of the pandemic declaration, vaccine companies had developed, produced, and distributed hundreds of millions of doses of licensed pandemic vaccines. Unfortunately, the response was not fast enough as substantial vaccine quantities were available only after the second pandemic wave had peaked. This delay was at least partially due to the late availability of a high-yielding influenza strain which could be used for vaccine production.
One way of obtaining a high-yielding influenza strain is to reassort the circulating vaccine strain with a faster-growing high-yield donor strain. This can be achieved by co-infecting a culture host with the circulating influenza strain and the high-yield donor strain and selecting for reassortant viruses which contain the hemagglutinin (HA) and neuraminidase (NA) segments from the vaccine strain and the other viral segments (i.e. those encoding PB1, PB2, PA, NP, M1, M2, NS1 and NS2) from the donor strain. Another approach is to reassort the influenza viruses by reverse genetics (see, for example references 1 and 2).
As the 2009 experience has shown, the traditional methods for reassorting influenza viruses may not be fast enough to provide sufficient amounts of influenza vaccine during a pandemic. In particular, valuable time is lost in preparing the high-yielding seed virus. There is therefore still a need in the art to provide methods which allow the rapid generation of high-yielding seed viruses in order to further decrease the time it takes between the emergence of an influenza pandemic and the provision of an influenza vaccine. The prior art had suggested solving this problem by preparing HA segments synthetically (see, for example, references 3, 4 and 5). The fastest reported time frame in which the influenza viruses can be prepared using these methods is nine days. Furthermore, these techniques rely on the use of 293T cells which have a high transfection efficacy but which are not approved for vaccine manufacture. There is therefore a need in the art to provide further and improved methods for preparing reassortant influenza viruses.